Contribution of chemokine CCL2/CCR2 signaling in the dorsal root ganglion and spinal cord to the maintenance of neuropathic pain in a rat model of lumbar disc herniation

Abstract

Lumbar disc herniation (LDH) is a major cause of sciatica and the underlying mechanisms are not well understood. Chemokine CCL2 has been implicated to play a vital role in the neuroinflammation and central sensitization after spinal nerve ligation. Here we investigated the expression and the role of CCL2 and its receptor CCR2 in LDH-induced pain. Implantation of autologous nucleus pulposus (NP) induced persistent pain hypersensitivity, associated with increased mRNA expression of CCL2 and CCR2 in the DRG and spinal cord. Interestingly, CCL2 was increased in neurons and CCR2 was mainly increased in macrophages in the DRG, whereas CCL2 and CCR2 were increased in astrocytes and neurons, respectively in the spinal cord. Intrathecal injection of CCR2 antagonist, RS504393 at 3 days or 10 days significantly attenuated NP-induced mechanical allodynia. The results suggest that CCL2/CCR2 in the DRG and spinal cord is involved in the maintenance of LDH-induced pain . Targeting CCL2/CCR2 signaling may be a potential treatment for chronic radicular neuropathic pain.

PERSPECTIVE:

These results suggest that CCL2/CCR2 signaling in the DRG and spinal cord is involved in LDH-induced pain via distinct mechanisms. These findings provide evidence of the antinociceptive effect of CCR2 antagonist on radicular neuropathic pain.

Copyright © 2014 American Pain Society. Published by Elsevier Inc. All rights reserved.

KEYWORDS:

CCL2, CCR2, astrocytes, chemokines, lumber disc herniation, neuronal-glial interaction

PMID:

 

24462503

 

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